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Study of Drug Exposure in Systemic Circulation of Primatene Mist by Oral Inhalation, Versus Epinephrine Injection by Intramuscular Injection and ProAir by Oral Inhalation in Healthy Individuals

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04207840
Recruitment Status : Completed
First Posted : December 23, 2019
Last Update Posted : July 8, 2020
Sponsor:
Information provided by (Responsible Party):
Amphastar Pharmaceuticals, Inc.

Brief Summary:
To assess the drug exposure profile in systemic circulation of Primatene Mist by inhalation, versus Epinephrine by intramuscular injection, and ProAir HFA by inhalation in healthy adults.

Condition or disease Intervention/treatment Phase
Pharmacokinetics Epinephrine Albuterol Asthma Anaphylaxis Combination Product: Epinephrine (0.125 mg/inhalation) Combination Product: Epinephrine Injection Auto-Injector (0.3mg/0.3mL) Combination Product: Albuterol Sulfate (0.09 mg/inhalation) Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 28 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Investigator)
Primary Purpose: Treatment
Official Title: Study of Drug Exposure in Systemic Circulation of Primatene Mist (0.25mg) by Oral Inhalation, Versus Epinephrine Injection (0.30mg) by Intramuscular Injection and ProAir (0.18mg) by Oral Inhalation in Healthy Individuals: A Randomized, Safety Evaluator-blind, Three-Treatment, Crossover, Fasting Study
Actual Study Start Date : December 9, 2019
Actual Primary Completion Date : December 20, 2019
Actual Study Completion Date : December 23, 2019


Arm Intervention/treatment
Experimental: Primatene Mist, E004
Participants who dosed with Primatene Mist.
Combination Product: Epinephrine (0.125 mg/inhalation)
Participants will self-administer 2 inhalations of Epinephrine (0.125 mg/inhalation) for a total dosage of 0.25 mg.
Other Name: Primatene Mist

Active Comparator: Epinephrine Injection Auto-Injector (Generic of EpiPen)
Participants who were dosed with an Epinephrine Injection Auto-Injector.
Combination Product: Epinephrine Injection Auto-Injector (0.3mg/0.3mL)
Participants will receive an intramuscular injection of Epinephrine via Auto-Injector (0.30 mg of epinephrine solution in 0.30 mL). The 0.30 mL dose will be given perpendicularly as a single deep intramuscular injection into the anterolateral aspect of the thigh.
Other Name: Generic of EpiPen

Active Comparator: Albuterol HFA
Participants who dosed with Albuterol HFA.
Combination Product: Albuterol Sulfate (0.09 mg/inhalation)
Participants will self-administer 2 inhalations of Albuterol Sulfate (0.09 mg/inhalation) for a total dosage of 0.18 mg.
Other Name: Albuterol HFA




Primary Outcome Measures :
  1. Area Under the Curve (AUC) of Epinephrine Plasma Concentration from time 0 to 6 hours post-dose, AUC[0-6h] [ Time Frame: From 30 minutes before dose until 24 hours after dose ]
    Pharmacokinetic (PK) blood samples will be collected starting 30 minutes before dose and until 24 hours after dose. Plasma will be isolated for analyzing the concentrations of Albuterol and Epinephrine. AUC[0-6h] will be calculated with the trapezoid method.

  2. Area Under the Curve (AUC) of Albuterol Plasma Concentration from time 0 to 24 hours post-dose, AUC[0-24h] [ Time Frame: From 30 minutes before dose until 24 hours after dose ]
    Pharmacokinetic (PK) blood samples will be collected starting 30 minutes before dose and until 24 hours after dose. Plasma will be isolated for analyzing the concentrations of Albuterol and Epinephrine. AUC[0-24h] will be calculated with the trapezoid method.

  3. Area Under the Curve (AUC) of Albuterol or Epinephrine Plasma Concentration from time 0 to infinity, AUC[0-inf] [ Time Frame: From 30 minutes before dose until 24 hours after dose ]
    Pharmacokinetic (PK) blood samples will be collected starting 30 minutes before dose and until 24 hours after dose. Plasma will be isolated for analyzing the concentrations of Albuterol and Epinephrine. AUC[0-inf] will be calculated with the extrapolation method.

  4. Maximum Plasma Concentration of Albuterol or Epinephrine, C[max] [ Time Frame: From 30 minutes before dose until 24 hours after dose ]
    Pharmacokinetic (PK) blood samples will be collected starting 30 minutes before dose and until 24 hours after dose. Plasma will be isolated for analyzing the concentrations of Albuterol and Epinephrine. C[max] will be obtained directly from the plot of PK curve.


Secondary Outcome Measures :
  1. Time at which Maximum Plasma Concentration of Albuterol or Epinephrine is observed, t[max] [ Time Frame: From 30 minutes before dose until 24 hours after dose ]
    Pharmacokinetic (PK) blood samples will be collected starting 30 minutes before dose and until 24 hours after dose. Plasma will be isolated for analyzing the concentrations of Albuterol and Epinephrine. t[max] will be obtained directly from the plot of PK curve when the maximum concentration is observed.

  2. Terminal Elimination Half-life of Albuterol or Epinephrine, T[1/2] [ Time Frame: From 30 minutes before dose until 24 hours after dose ]
    Pharmacokinetic (PK) blood samples will be collected starting 30 minutes before dose and until 24 hours after dose. Plasma will be isolated for analyzing the concentrations of Albuterol and Epinephrine.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Agree to participate; understand and sign informed consent;
  • Male and female adults, aged 18 to 50 years, inclusive at Screening;
  • Generally healthy and medically stable, with no clinically significant abnormalities based on physical examination and laboratory tests as determined by the Investigators;
  • Have good venous access;
  • Have normal resting blood pressure and normal heart rate (HR) without history of syncope; a subject with out of range blood pressure may be enrolled in the study at the discretion of the Principal Investigator;
  • Have a body mass index (BMI) of 18.0 - 30.0 kg/m^2;
  • Female candidates must be >1 year post-menopausal or practicing a clinically acceptable form of birth control and confirmed by negative urine or serum pregnancy test at Screening;
  • Negative HIV-Ab, HBs-Ag and HCV-Ab;
  • Negative alcohol test (urine or breathalyzer);
  • Negative drug screening results;
  • Currently non-smoker; have not used any tobacco products for at least three (3) months prior to Screening; and
  • Demonstrate proficiency in the use of MDI and a consistent inhalation time >2.0 seconds after training, for at least three (3) times, with a maximum of 5 attempts.

Exclusion Criteria:

  • Concurrent clinically significant cardiovascular, hematological, renal, neurologic, hepatic, endocrine, psychiatric, or malignant diseases.
  • Known intolerance or hypersensitivity to any component of the study drugs (i.e., Epinephrine, Albuterol Sulfate or any sympathomimetic drugs, HFA-134a, thymol, ethanol, ascorbic acid, nitric acid, and hydrochloric acid).
  • Upper or lower respiratory tract infection, or other systemic infection within 6 weeks prior to Screening;
  • Clinically significant abnormalities in the screening/baseline ECG; prolonged corrected QT interval (QTcF) on ECG: men >450ms, women: >470ms; single or multiple premature ventricular contractions (PVC);
  • Abnormal thyroid function test (if TSH is out of range, refer to T3/T4 for thyroid function assessment);
  • Subject has been on other investigational drug/device studies within 30 days of Screening Visit or planned participation in another investigational drug trial at any time during this trial;
  • Women who are pregnant or lactating or planning a pregnancy during the study period;
  • Subject has donated or lost > 500 mL of blood within 3 months of Screening;
  • Evidence of alcohol or drug abuse or dependency within 6 months prior to screening; or
  • Use of any of the prohibited drugs without appropriate washout.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04207840


Locations
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United States, California
Amphastar Study Site 0035
Cypress, California, United States, 90630
Sponsors and Collaborators
Amphastar Pharmaceuticals, Inc.
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Responsible Party: Amphastar Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT04207840    
Other Study ID Numbers: API-E004-CL-I
First Posted: December 23, 2019    Key Record Dates
Last Update Posted: July 8, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Access to patient level data and supporting clinical documents may be requested by qualified researchers. Requests will be reviewed on the basis of scientific merit. Patient data will be de-identified to protect the privacy of trial patients in line with applicable laws and regulations.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Respiratory Aspiration
Anaphylaxis
Respiration Disorders
Respiratory Tract Diseases
Pathologic Processes
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Epinephrine
Racepinephrine
Albuterol
Epinephryl borate
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Adrenergic beta-Agonists
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Respiratory System Agents
Mydriatics
Sympathomimetics
Vasoconstrictor Agents
Tocolytic Agents
Reproductive Control Agents
Adrenergic beta-2 Receptor Agonists